Joanne Mortimer, MD, medical oncologist, Baum Family Professor in Women’s Cancers, associate director, Education and Training, Comprehensive Cancer Center, vice chair and professor, Department of Medical Oncology and Therapeutics Research, director, Women’s Cancer Programs, City of Hope, discusses the potential benefit of tucatinib (Tukysa) plus antibody-drug conjugates (ADCs) in HER2-positive breast cancer.

Updated results of the phase 3 DESTINY-Breast03 trial (NCT03529110), which were presented during the 2021 San Antonio Breast Cancer Symposium, showed that fam-trastuzumab deruxtecan-nxki (Enhertu) may replace ado-trastuzumab emtansine (T-DM1; Kadcyla) as a second-line option for patients with metastatic HER2-positive breast cancer. However, clinical trials are currently ongoing that are evaluating the efficacy of tucatinib (Tukysa) plus trastuzumab deruxtecan (CompassHER2 RD; NCT04457596) and tucatinib plus T-DM1 (HER2CLIMB-04; NCT04539938). Notably, the study scheme of HER2CLIMB-04 were also presented during the 2021 SABCS. Ultimately, the results of these studies will demonstrate the feasibility of tucatinib plus ADCs in HER2-positive breast cancer.

Tucatinib and trastuzumab deruxtecan can confer limiting toxicities like diarrhea in patients with HER2-positive breast cancer. However, the field has become comfortable managing the toxicities associated with T-DM1 and patients can often remain on treatment for many years, Mortimer explains. As such, the data evaluating tucatinib plus ADCs will inform whether patients can derive benefit with the combination regimen and whether toxicity will factor into treatment selection, Mortimer concludes.

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Joanne Mortimer, MD, discusses the potential benefit of tucatinib plus antibody-drug conjugates in HER2-positive breast cancer.  



Dr. Mortimer on the Potential Benefit of Tucatinib Plus ADCs in HER2+ Breast Cancer 

Joanne Mortimer, MD, associate director for Education and Training, Comprehensive Cancer Center, Baum Family Professor in Women’s Cancers, vice chair and professor, Department of Medical Oncology and Therapeutics Research, director, Women’s Cancer Programs, and breast cancer oncologist, City of Hope, discusses brain metastases in women with HER2-positive breast cancer.

One of the continual challenges in HER2-positive breast cancer is disease that has metastasized to the brain, says Mortimer. Moreover, brain metastases seem to be more common in HER2-positive breast cancer than in some of the other subtypes.

As the lifespan of women with HER2-positive breast cancer increases, so does the chance of disease metastasizing to the brain. Currently, radiation and surgery are the staples of treatment for these women. However, new brain metastases may develop in the setting of prior radiation or in places that are inaccessible to radiation and surgery, explains Mortimer. For those women, there are some data to suggest that lapatinib (Tykerb) and neratinib (Nerlynx) have some activity. Additionally, ado-trastuzumab emtansine (T-DM1; Kadcyla) has been shown to cause regression of brain metastases in very small series, she adds.

One of the most promising agents under investigation is tucatinib (ONT-380). In the ongoing phase II HER2CLIMB trial, patients are randomized to receive tucatinib with capecitabine and trastuzumab (Herceptin) or capecitabine and trastuzumab alone. Tucatinib is unique in that it is a selective HER2 drug that has been shown to have some activity in preventing and targeting brain metastases, concludes Mortimer.

Dr. Mortimer on Brain Metastases in HER2+ Breast Cancer

Joanne Mortimer, MD, associate director for Education and Training, Comprehensive Cancer Center, Baum Family Professor in Women’s Cancers, vice chair and professor, Department of Medical Oncology & Therapeutics Research, director, Women’s Cancer Programs, City of Hope, discusses adjuvant therapy in early-stage HER2-positive breast cancer.

One of the challenges in this setting is figuring out whether there is a role for pertuzumab (Perjeta), says Mortimer. The phase III APHINITY trial looked at adjuvant trastuzumab (Herceptin) and chemotherapy with or without pertuzumab. However, the majority of patients who enrolled in the trial had negative nodes and therein a favorable outcome, she says. Now, these women would likely be treated with paclitaxel and trastuzumab without any consideration of additional adjuvant therapy.

The results of the randomized study did not show a significant advantage with the addition of pertuzumab to trastuzumab. However, there did appear to be a benefit in the subset of patients who had positive lymph nodes. Therefore, in patients with negative lymph nodes, the addition of pertuzumab is probably not needed in the adjuvant setting. Based on these data, this approach may be worth considering for those with positive lymph nodes, Mortimer concludes.

Joanne Mortimer, MD

Articles

Dr. Mortimer on the Potential Benefit of Tucatinib Plus ADCs in HER2+ Breast Cancer

Dr. Mortimer on Brain Metastases in HER2+ Breast Cancer

Dr. Mortimer on Adjuvant Therapy in Early-Stage HER2+ Breast Cancer